title: Targeted glycoproteomic analysis reveals that kappa-5 is a major, uniquely glycosylated component of Schistosoma mansoni egg antigens.
abstract: Glycans present on glycoproteins from the eggs of the parasite Schistosoma mansoni are mediators of various immune responses of the human host, including T-cell modulation and granuloma formation, and they are the target of glycan-specific antibodies. Here we have analyzed the glycosylation of kappa-5, a major glycoprotein antigen from S. mansoni eggs using a targeted approach of lectin purification followed by mass spectrometry of glycopeptides as well as released glycans. We demonstrate that kappa-5 has four fully occupied N-glycosylation sites carrying unique triantennary glycans composed of a difucosylated and xylosylated core region, and immunogenic GalNAcβ1-4GlcNAc (LDN) termini. Furthermore, we show that the kappa-5 specific IgE antibodies in sera of S. mansoni-infected individuals are directed against the core region of the kappa-5 glycans. Whereas two previously analyzed immunomodulatory egg glycoproteins, IPSE/alpha-1 and omega-1, both express diantennary N-glycans with a difucosylated core and one or two Galβ1-4(Fucα1-3)GlcNAc (Lewis X) antennae, the kappa-5 glycosylation appears unique among the major soluble egg antigens of S. mansoni. The distinct structural and antigenic properties of kappa-5 glycans suggest a specific role for kappa-5 in schistosome egg immunogenicity.
authors.affiliation: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: Moniek H J
authors.initials: MH
authors.lastname: Meevissen
authors.forename: Crina I A
authors.initials: CI
authors.lastname: Balog
authors.forename: Carolien A M
authors.initials: CA
authors.lastname: Koeleman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Doenhoff
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schramm
authors.forename: Helmut
authors.initials: H
authors.lastname: Haas
authors.forename: André M
authors.initials: AM
authors.lastname: Deelder
authors.forename: Manfred
authors.initials: M
authors.lastname: Wuhrer
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Hokke
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood* / Q000737:chemistry; D000947:Antigens, Helminth; D004527:Egg Proteins / Q000276:immunology / Q000378:metabolism*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000737:chemistry; D006031:Glycosylation; D015801:Helminth Proteins / Q000276:immunology / Q000378:metabolism*; D006790:Host-Parasite Interactions; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000737:chemistry; D007785:Lactose / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry; D012550:Schistosoma mansoni / Q000276:immunology / Q000378:metabolism*; D012555:Schistosomiasis mansoni / Q000097:blood* / Q000276:immunology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D004527:Egg Proteins; D006023:Glycoproteins; D015801:Helminth Proteins; D010446:Peptide Fragments; D011134:Polysaccharides; C093701:N-acetylgalactosaminyl-1-4-N-acetylglucosamine; D007073:Immunoglobulin E; D006026:Glycoside Hydrolases; D007785:Lactose